Hyperuricemia is defined by blood uric acid value of more than 6.8 to 7.0 mg/dl in men or more than 6.0 mg/dl in women. In the United State, approximately 3 million to 5 million people suffer from hyperuricemia and metabolism disorders related with hyperuricemia (e.g., gout). The possibility of having gout by African Americans is two times the Caucasians in the United States. Gout and hyperuricemia are also very widely spread in China, Japan, Polynesian countries, and Sub-Saharan Africa. Between 1990 and 2010, occurrence rate of gout has increased by 2 times, and number of the gout patient tends to increase by 14% on average per year in South Korea.
Examples of the metabolism disorders related with hyperuricemia include not only gout but also uric acid crystals, precipitation of uric acid crystals in joint, acute monoarticular arthritis caused by precipitation of uric acid crystals in kidney tissues, pain crisis of inflammatory arthritis, urinary tract stone, renal stone, and gouty nephropathy. Chronic renal stone and gouty nephropathy are known to increase the risk of having kidney damage and renal failure. Among the metabolic disorders related with hyperuricemia, gout is a disease by which, in accordance with increased concentration of uric acid in blood (i.e., waste product of purine which has been taken from foods, i.e., waste product of the metabolism by human body), uric acid salts are precipitated in cartilage, tendon, or peripheral tissues (i.e., in blood, body fluid, and joint fluid, uric acid is present in the form of uric acid salts). Those phenomena cause joint inflammation to yield a recurrent crisis accompanying severe pain, and, according to precipitation of gouty tophi resulting from uric acid crystals, a deformation and a damage in joint are yielded. Other than the problems in joint, various renal disorders are also caused and nephrolithiasis (i.e., lithonephria) by which stones are formed inside a kidney due to the uric acid may be caused.
Furthermore, gout is exhibited with steps like asymptomatic hyperuricemia, acute gouty arthritis, interval gout, chronic tophaceous gout, and the like. The asymptomatic hyperuricemia which appears at an early stage indicates a state in which, although there is an increase in blood uric acid concentration, symptoms like arthritis, gouty tophi, and uric acid nephrolithiasis are not exhibited yet. Acute gouty arthritis is a stage in which, after hyperuricemia which generally continues at least for 20 years, a gouty crisis or nephrolithiasis occurs. The most characteristic symptom is acute crisis of very painful arthritis. At an early stage, a single joint may be invaded without having a systemic symptom, but, more and more joints may be gradually invaded along with high fever. The interval gout indicates a period in which there is no symptom between gouty crises. In most cases, the second crisis occurs between 6 months and 2 years after having the first crisis. Although it may vary depending on the treatment, frequency of the crisis gradually increases, thus yielding invasion into many joints. Chronic tophaceous gout is similarly shown like other arthritis once the symptom is developed to a chronic tophaceous gout stage after the interval period having no gout. Gradual stiffness and continuous pain occur in an invaded joint.
Although gout is known as a disorder which has a clearly established therapy and can be successfully cured, as there are many cases in which it is accompanied with other disorders like high blood pressure and chronic renal failure, careful consideration regarding side effects of pharmaceuticals is often needed, and, as a non-pharmaceutical treatment, efforts of a patient to change his lifestyle are essential for having favorable prognosis of a long-term treatment. Gout and hyperuricemia show clinical conditions like high blood pressure, hyperlipidemia, increased blood sugar level, abdominal obesity, or the like, and although they do not fall into the category of diagnosis standards of metabolic syndrome, which is complex conditions that can bring increased risk of having an adult disease like arteriosclerotic heart disease and type 2 diabetes, they are believed to have a close relationship with a metabolic syndrome. It has been reported that 44% of the gout patients in South Korea also have a metabolic syndrome. Although gout is generally exhibited in the form of acute monoarthritis, a few joints may be invaded, or, in rare case, several joints are invaded by gout. It is well known that non-steroidal anti-inflammatory drugs (NSAIDs), which are used for a treatment of acute gout, can suppress an inflammatory response. Both colchicines and steroids, which exhibit an anti-inflammatory activity by suppressing the activity and movement of white blood cells, are a pharmaceutical that can effectively treat gout crisis. It is known that a selective cyclooxygenase (COX-2) inhibitor also has the same effect as existing NSAIDs.
Furthermore, if the blood uric acid concentration is maintained at saturation state or lower level for a long period of time, not only the acute gouty arthritis can be prevented but also the size of previously-formed gouty tophi can be reduced. For a treatment of lowering the blood uric acid concentration at chronic stage of gout, two main kinds of a uric acid lowering agent are used, i.e., xanthine oxidase (XO) inhibitor and uricosuric agent. As for an inhibitor for uric acid synthesis, there is allopurinol which has been conventionally used and febuxostat which has been recently developed as a new pharmaceutical. Allopurinol is an XO inhibitor which can be effectively used regardless of the cause of hyperuricemia. However, the most significant side effect of allopurinol is hypersensitivity syndrome, and, with exhibition of high fever, erythema, increased eosinophils, hepatitis, renal failure or the like, it is known to have a risk of causing death. Febuxostat is also an oxidase inhibitor, but, unlike allopurinol, it is mainly metabolized in liver as a non-purine-based selective blocker, and generates glucuronide. Most gout cases progress into chronic gout, and for those cases, an anti-inflammatory preparation and a treatment of reducing uric acid concentration are given as a preventive measure even when there is no symptom. The preventive treatment should be carried out only after the disease is maintained in a moderate state for a certain period of time. If not, gout may recur in more severe form. However, the suitable moderate period of disease is still controversial, and suppressing an abrupt onset of gout, which recurs intermittently, by a preventive treatment cannot be achieved with pharmaceuticals which have been developed until now. In addition, the technique for inhibiting the oxidase as a gout-inducing enzyme by using natural products remains insufficient at present moment.
Meanwhile, Alpinia oxyphylla is a fruit of Zingiberaceae, and it naturally grows in Haenamsung and Kawndong area in China. Alpinia oxyphylla has both ends with slightly sharp globular or elliptical shape with length of 1 to 2 cm and diameter of 7 to 10 mm. The outside has brown to dark brown color and has several small bump-like protruded lines that are longitudinally connected to each other. Thickness of the fruit skin is 0.3 to 0.5 mm, and as the fruit skin is tightly adhered to a seed lump, it is difficult to peel the skin. Inside of the fruit is divided into three sections by thin membrane, and 5 to 8 seeds, which adhere to one another via a pseudo seed coat, are present in each section. The seed has brown to dark brown color, and, as an irregular polyhedron, it has diameter of about 3.5 mm and hard texture. It has unique smell and slightly bitter taste. As known components of Alpinia oxyphylla, it is believed that nootkatone, epinootkatol, β-nootkatol, β-pinene, p-cymene, terpinen-4-ol, yakuchinone A and B, which are a diarylheptanoid compound, and tectochrysin, chrysin, izalpinin, and 3,5-dihydroxy-7,4′-dimethoxyflavone as a flavonoid component are contained. Nootkatone has an anti-stomach ulcer activity, and yakuchinone A and B have an anti-inflammation activity and can suppress an occurrence of skin cancer and lower the expression of COX-2 and iNOS and the activity of NFκB. Other than those, it is also known that yakuchinone A, nootkatone, and epinootkatol have an insecticidal effect, and they are also known to exhibit an activity of protecting brain cells, an anti-allergy activity, a skin whitening activity, or the like.
It is also known that essential oil components of Alpinia oxyphylla can increase the skin permeability of pharmaceuticals, exhibit an activity of relaxing smooth muscle and suppressing cardiac muscle by suppressing competitively the introduction of calcium ions into a cell, and also have an anti-diuretic activity, an anti-ulcer activity, an anti-dementia activity, and an activity of improving learning abilities.
As a technique relating to an extract of Alpinia oxyphylla or hyperuricemia, a method and a composition for treating hyperuricemia and a disorder related with hyperuricemia is described in Korean Patent Registration No. 1567885. In Korean Patent Application Publication No. 2006-0120791, a pharmaceutical composition for improving lipid metabolism and preventing and treating obesity comprising an extract of Alpinia oxyphylla is disclosed. In Korean Patent Application Publication No. 1992-0011502, an improved oriental therapeutic material of Bujaeejoongtang for treating pains of a human neural system is disclosed.
However, the composition for preventing, ameliorating, or treating hyperuricemia or metabolic disorders related with hyperuricemia of the present invention, which comprises an extract of Alpinia oxyphylla as an effective ingredient, has not been disclosed.